tbuckley/cabot-search huggingface dataset:
Engineering poly- and micelleplexes for nucleic acid delivery – A reflection on their endosomal escape
Authors: Benjamin Winkeljann, David C. Keul, Olivia M. Merkel
Journal: Journal of Controlled Release (2022)

For the longest time, the field of nucleic acid delivery has remained skeptical whether or not polycationic drug carrier systems would ever make it into clinical practice. Yet, with the disclosure of patents on polyethyleneimine-based RNA carriers through leading companies in the field of nucleic acid therapeutics such as BioNTech SE and the progress in clinical studies beyond phase I trials, this aloofness seems to regress. As one of the most striking characteristics of polymer-based vectors, the extraordinary tunability can be both a blessing and a curse. Yet, knowing about the adjustment screws and how they impact the performance of the drug carrier provides the formulation scientist committed to its development with a head start. Here, we equip the reader with a toolbox - a toolbox that should advise and support the developer to conceptualize a cutting-edge poly- or micelleplex system for the delivery of therapeutic nucleic acids; to be specific, to engineer the vector towards maximum endosomal escape performance at minimum toxicity. Therefore, after briefly sketching the boundary conditions of polymeric vector design, we will dive into the topic of endosomal trafficking. We will not only discuss the most recent knowledge of the endo-lysosomal compartment but further depict different hypotheses and mechanisms that facilitate the endosomal escape of polyplex systems. Finally, we will combine the different facets introduced in the previous chapters with the fundamental building blocks of polymer vector design and evaluate the advantages and drawbacks. Throughout the article, a particular focus will be placed on cellular peculiarities, not only as an additional barrier, but also to give inspiration to how such cell-specific traits might be capitalized on.
Development of poly(lactide-co-glycolide) microparticles for sustained delivery of meloxicam
Authors: Yihua Pei, Jianping Wang, Nisar Ul Khaliq, Fanfei Meng, Kaoutar A. Oucherif, Jie Xue, Sarena D. Horava, Amy L. Cox, Coralie A. Richard, Monica R. Swinney, Kinam Park, Yoon Yeo
Journal: Journal of Controlled Release (2022)
Mucus adhesion vs. mucus penetration? Screening nanomaterials for nasal inhalation by MD simulation
Authors: Xiaoshu Gao, Yin Xiong, Hening Chen, Xuheng Gao, Jiaxin Dai, Yutong Zhang, Wanhang Zou, Yang Gao, Zhenyan Jiang, Bing Han
Journal: Journal of Controlled Release (2022)
Evaluation in pig of an intestinal administration device for oral peptide delivery
Authors: Staffan Berg, Teresia Uggla, Malin Antonsson, Sandro Filipe Nunes, Maria Englund, Louise Rosengren, Masoud Fahraj, Xiaoqiu Wu, Rydvikha Govender, Magnus Söderberg, David Janzén, Natalie Van Zuydam, Andreas Hugerth, Anette Larsson, Susanna Abrahmsén-Alami, Bertil Abrahamsson, Nigel Davies, Christel A.S. Bergström
Journal: Journal of Controlled Release (2022)
Applications of polydopaminic nanomaterials in mucosal drug delivery
Authors: Takwa Bedhiafi, Sourour Idoudi, Areej Ali Alhams, Queenie Fernandes, Heba Iqbal, Renuka Basineni, Shahab Uddin, Said Dermime, Maysaloun Merhi, Nashiru Billa
Journal: Journal of Controlled Release (2022)

Polydopamine (PDA) is a biopolymer with unique physicochemical properties, including free-radical scavenging, high photothermal conversion efficiency, biocompatibility, biodegradability, excellent fluorescent and theranostic capacity due to their abundant surface chemistry. Thus, PDA is used for a myriad of applications including drug delivery, biosensing, imaging and cancer therapy. Recent reports present a new functionality of PDA as a coating nanomaterial, with major implications in mucosal drug delivery applications, particularly muco-adhesion and muco-penetration. However, this application has received minimal traction in the literature. In this review, we present the physicochemical and functional properties of PDA and highlight its key biomedical applications, especially in cancer therapy. A detailed presentation of the role of PDA as a promising coating material for nanoparticulate carriers intended for mucosal delivery forms the core aspect of the review. Finally, a reflection on key considerations and challenges in the utilizing PDA for mucosal drug delivery, along with the possibilities of translation to clinical studies is expounded.
A novel peptide hydrogel of metal ion clusters for accelerating bone defect regeneration
Authors: Liu Xu, Shan Xu, Tang Yong Xiang, Lin Wei Chen, Wei Xi Zhong, Ling Zhu, Heng Liu, Li Wu, Wei Dong Li, Yu Tong Wang, Bao Chang Cai, Jun Hong Yao, Rui Chen, Wen Feng Xin, Gang Cao, Zhi Peng Chen
Journal: Journal of Controlled Release (2022)
Exosomes-mediated tumor metastasis through reshaping tumor microenvironment and distant niche
Authors: Xinyi Luo, Yang Li, Zhenglai Hua, Xiaoxia Xue, Xiangpeng Wang, Mingshi Pang, Cheng Xiao, Hongyan Zhao, Aiping Lyu, Yuanyan Liu
Journal: Journal of Controlled Release (2022)
Hydroxyethyl starch-folic acid conjugates stabilized theranostic nanoparticles for cancer therapy
Authors: Chong Wang, Qiang Wang, Huimin Wang, Zheng Li, Jitang Chen, Zhijie Zhang, Haowen Zeng, Ximiao Yu, Xiaoquan Yang, Xiangliang Yang, Zifu Li
Journal: Journal of Controlled Release (2022)
LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice
Authors: Megan Mulholland, Eva Kritikou, Pernilla Katra, Jan Nilsson, Harry Björkbacka, Andrew H. Lichtman, Annabelle Rodriguez, Daniel Engelbertsen
Journal: JACC CardioOncology (2022)

The immune checkpoint receptor lymphocyte-activation gene 3 (LAG3) is a new target for immune checkpoint blockade (ICB), but the effects of LAG3 on atherosclerosis are not known.
Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis
Authors: Khushpreet Kaur, Sumedha Sharma, Sudhanshu Abhishek, Prabhdeep Kaur, Uttam Chand Saini, Mandeep Singh Dhillon, Petros C. Karakousis, Indu Verma
Journal: Journal of Infection (2022)
Elastin-like polypeptide-based micelles as a promising platform in nanomedicine
Authors: Jolinde van Strien, Oscar Escalona-Rayo, Wim Jiskoot, Bram Slütter, Alexander Kros
Journal: Journal of Controlled Release (2022)

New and improved nanomaterials are constantly being developed for biomedical purposes. Nanomaterials based on elastin-like polypeptides (ELPs) have increasingly shown potential over the past two decades. These polymers are artificial proteins of which the design is based on human tropoelastin. Due to this similarity, ELP-based nanomaterials are biodegradable and therefore well suited to drug delivery. The assembly of ELP molecules into nanoparticles spontaneously occurs at temperatures above a transition temperature (Tt). The ELP sequence influences both the Tt and the physicochemical properties of the assembled nanomaterial. Nanoparticles with desired properties can hence be designed by choosing the appropriate sequence. A promising class of ELP nanoparticles are micelles assembled from amphiphilic ELP diblock copolymers. Such micelles are generally uniform and well defined. Furthermore, site-specific attachment of cargo to the hydrophobic block results in micelles with the cargo shielded inside their core, while conjugation to the hydrophilic block causes the cargo to reside in the corona where it is available for interactions. Such control over particle design is one of the main contributing factors for the potential of ELP-based micelles as a drug delivery system. Additionally, the micelles are easily loaded with protein or peptide-based cargo by expressing it as a fusion protein. Small molecule drugs and other cargo types can be either covalently conjugated to ELP domains or physically entrapped inside the micelle core. This review aims to give an overview of ELP-based micelles and their applications in nanomedicine.
The Role of Single-Cell Profiling and Deep Immunophenotyping in Understanding Immune Therapy Cardiotoxicity
Authors: Yuhsin Vivian Huang, Sarah Waliany, Daniel Lee, Francisco X Galdos, Ronald M Witteles, Joel W Neal, Alice C Fan, Holden T Maecker, Patricia K Nguyen, Sean M Wu, Han Zhu
Journal: JACC CardioOncology (2022)
Cardiotoxicity of T-Cell Antineoplastic Therapies
Authors: Sarju Ganatra, Sourbha S. Dani, Eric H. Yang, Vlad G. Zaha, Anju Nohria
Journal: JACC CardioOncology (2022)

T-cell therapies, such as chimeric antigen receptor (CAR) T-cell, bispecific T-cell engager (BiTE) and tumor-infiltrating lymphocyte (TIL) therapies, fight cancer cells harboring specific tumor antigens. However, activation of the immune response by these therapies can lead to a systemic inflammatory response, termed cytokine release syndrome (CRS), that can result in adverse events, including cardiotoxicity. Retrospective studies have shown that cardiovascular complications occur in 10% to 20% of patients who develop high-grade CRS after CAR T-cell therapy and can include cardiomyopathy, heart failure, arrhythmias, and myocardial infarction. While cardiotoxicities have been less commonly reported with BiTE and TIL therapies, systematic surveillance for cardiotoxicity has not been performed. Patients undergoing T-cell therapies should be screened for cardiovascular conditions that may not be able to withstand the hemodynamic perturbations imposed by CRS. Generalized management of CRS, including the use of the interleukin-6 antagonist, tocilizumab, for high-grade CRS, is used to mitigate the risk of cardiotoxicity.
Inhaled dry powder cisplatin increases antitumour response to anti-PD1 in a murine lung cancer model
Authors: Tamara Davenne, Pauline Percier, Lionel Larbanoix, Muriel Moser, Oberdan Leo, Etienne Meylan, Stanislas Goriely, Pierre Gérard, Nathalie Wauthoz, Sophie Laurent, Karim Amighi, Rémi Rosière
Journal: Journal of Controlled Release (2022)

Despite advances in targeted therapies and immunotherapy in lung cancer, chemotherapy remains the backbone of treatment in most patients at different stages of the disease. Inhaled chemotherapy is a promising strategy to target lung tumours and to limit the induced severe systemic toxicities. Cisplatin dry powder for inhalation (CIS-DPI) was tested as an innovative way to deliver cisplatin locally via the pulmonary route with minimal systemic toxicities. In vivo, CIS-DPI demonstrated a dose-dependent antiproliferative activity in the M109 orthotopic murine lung tumour model and upregulated the immune checkpoint PD-L1 on lung tumour cells. Combination of CIS-DPI with the immune checkpoint inhibitor anti-PD1 showed significantly reduced tumour size, increased the number of responders and prolonged median survival over time in comparison to the anti-PD1 monotherapy. Furthermore, the CIS-DPI and anti-PD1 combination induced an intra-tumour recruitment of conventional dendritic cells and tumour infiltrating lymphocytes, highlighting an anti-tumour immune response. This study demonstrates that combining CIS-DPI with anti-PD1 is a promising strategy to improve lung cancer therapy.
Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor–Induced Myocarditis
Authors: Alexi Vasbinder, YeeAnn Chen, Adrien Procureur, Allison Gradone, Tariq U. Azam, Daniel Perry, Husam Shadid, Elizabeth Anderson, Tonimarie Catalan, Pennelope Blakely, Namratha Nelapudi, Mohamad Fardous, Marie C. Bretagne, Sarah K. Adie, Kristen T. Pogue, Monika Leja, Sarah Yentz, Bryan Schneider, Leslie A. Fecher, Christopher D. Lao, Joe-Elie Salem, Salim S. Hayek
Journal: JACC CardioOncology (2022)
Pre-Existing Autoimmune Disease Increases the Risk of Cardiovascular and Noncardiovascular Events After Immunotherapy
Authors: Charlotte Lee, Zsofia D. Drobni, Amna Zafar, Carlos A. Gongora, Daniel A. Zlotoff, Raza M. Alvi, Jana Taron, Paula K. Rambarat, Sara Schoenfeld, Ramya C. Mosarla, Vineet K. Raghu, Sarah E. Hartmann, Hannah K. Gilman, Sean P. Murphy, Ryan J. Sullivan, Alexander Faje, Udo Hoffmann, Lili Zhang, Thomas Mayrhofer, Kerry L. Reynolds, Tomas G. Neilan
Journal: JACC CardioOncology (2022)
Longitudinal Strain and Troponin I Elevation in Patients Undergoing Immune Checkpoint Inhibitor Therapy
Authors: Yudai Tamura, Yuichi Tamura, Ryo Takemura, Kenta Yamada, Hirohisa Taniguchi, Jin Iwasawa, Hirotaka Yada, Akio Kawamura
Journal: JACC CardioOncology (2022)
“Swiss Army Knife” black phosphorus-based nanodelivery platform for synergistic antiparkinsonian therapy via remodeling the brain microenvironment
Authors: Guowang Cheng, Zhongjun Li, Yujing Liu, Rui Ma, Xiaojia Chen, Wen Liu, Yafang Song, Yuan Zhang, Guangtao Yu, Zhenfeng Wu, Tongkai Chen
Journal: Journal of Controlled Release (2022)
Hepatic targeting of the centrally active cannabinoid 1 receptor (CB1R) blocker rimonabant via PLGA nanoparticles for treating fatty liver disease and diabetes
Authors: Shira Hirsch, Liad Hinden, Meital Ben-David Naim, Saja Baraghithy, Anna Permyakova, Shahar Azar, Taher Nasser, Emma Portnoy, Majd Agbaria, Alina Nemirovski, Gershon Golomb, Joseph Tam
Journal: Journal of Controlled Release (2022)

Over-activation of the endocannabinoid/CB1R system is a hallmark feature of obesity and its related comorbidities, most notably type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD). Although the use of drugs that widely block the CB1R was found to be highly effective in treating all metabolic abnormalities associated with obesity, they are no longer considered a valid therapeutic option due to their adverse neuropsychiatric side effects. Here, we describe a novel nanotechnology-based drug delivery system for repurposing the abandoned first-in-class global CB1R antagonist, rimonabant, by encapsulating it in polymeric nanoparticles (NPs) for effective hepatic targeting of CB1Rs, enabling effective treatment of NAFLD and T2D. Rimonabant-encapsulated NPs (Rimo-NPs) were mainly distributed in the liver, spleen, and kidney, and only negligible marginal levels of rimonabant were found in the brain of mice treated by iv/ip administration. In contrast to freely administered rimonabant treatment, no CNS-mediated behavioral activities were detected in animals treated with Rimo-NPs. Chronic treatment of diet-induced obese mice with Rimo-NPs resulted in reduced hepatic steatosis and liver injury as well as enhanced insulin sensitivity, which were associated with enhanced cellular uptake of the formulation into hepatocytes. Collectively, we successfully developed a method of encapsulating the centrally acting CB1R blocker in NPs with desired physicochemical properties. This novel drug delivery system allows hepatic targeting of rimonabant to restore the metabolic advantages of blocking CB1R in peripheral tissues, especially in the liver, without the negative CB1R-mediated neuropsychiatric side effects.
Delayed Diagnosis and Recovery of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis on VA-ECMO Support
Authors: Tarun Ramayya, Joshua D. Mitchell, Justin C. Hartupee, Kory Lavine, Clare H. Ridley, Kunal D. Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A. Alvarez-Cardona, Ronald K. Krone, Courtney M. Campbell
Journal: JACC CardioOncology (2022)
Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines
Authors: Giulia Martina Cavestro, Alessandro Mannucci, Francesc Balaguer, Heather Hampel, Sonia S. Kupfer, Alessandro Repici, Andrea Sartore-Bianchi, Toni T. Seppälä, Vincenzo Valentini, Clement Richard Boland, Randall E. Brand, Tineke E. Buffart, Carol A. Burke, Riccardo Caccialanza, Renato Cannizzaro, Stefano Cascinu, Andrea Cercek, Emma J. Crosbie, Silvio Danese, Evelien Dekker, Maria Daca-Alvarez, Francesco Deni, Mev Dominguez-Valentin, Cathy Eng, Ajay Goel, Josè G. Guillem, Britt B.S.L. Houwen, Charles Kahi, Matthew F. Kalady, Fay Kastrinos, Florian Kühn, Luigi Laghi, Andrew Latchford, David Liska, Patrick Lynch, Alberto Malesci, Gianluca Mauri, Elisa Meldolesi, Pål Møller, Kevin J. Monahan, Gabriela Möslein, Caitlin C. Murphy, Karlijn Nass, Kimmie Ng, Cristina Oliani, Enrico Papaleo, Swati G. Patel, Marta Puzzono, Andrea Remo, Luigi Ricciardiello, Carla Ida Ripamonti, Salvatore Siena, Satish K. Singh, Zsofia K. Stadler, Peter P. Stanich, Sapna Syngal, Stefano Turi, Emanuele Damiano Urso, Laura Valle, Valeria Stella Vanni, Eduardo Vilar, Marco Vitellaro, Yi-Qian Nancy You, Matthew B. Yurgelun, Raffaella Alessia Zuppardo, Elena M. Stoffel
Journal: Clinical Gastroenterology and Hepatology (2022)

Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.
Role of wound microbiome, strategies of microbiota delivery system and clinical management
Authors: Qinghan Tang, Nannan Xue, Xiaofeng Ding, Kevin H.-Y. Tsai, Jonathan J. Hew, Ruihan Jiang, Rizhong Huang, Xuxi Cheng, Xiaotong Ding, Yuen Yee Cheng, Jun Chen, Yiwei Wang
Journal: Advanced Drug Delivery Reviews (2022)
Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Authors: A. Krämer, T. Bochtler, C. Pauli, G. Baciarello, S. Delorme, K. Hemminki, L. Mileshkin, H. Moch, K. Oien, T. Olivier, A. Patrikidou, H. Wasan, G. Zarkavelis, G. Pentheroudakis, K. Fizazi
Journal: Annals of Oncology (2022)
YAP regulates the liver size during the fasting-refeeding transition in mice
Authors: Xuan Li, Shicheng Fan, Chenghui Cai, Yue Gao, Xinhui Wang, Yifei Zhang, Hangfei Liang, Huilin Li, Jie Yang, Min Huang, Huichang Bi
Journal: Acta Pharmaceutica Sinica B (2022)

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.
Advancing detection and response capacities for emerging and re-emerging pathogens in Africa
Authors: Jean B Nachega, Sabin Nsanzimana, Angeli Rawat, Lindsay A Wilson, Philip J Rosenthal, Mark J Siedner, Jay K Varma, Peter H Kilmarx, Leon Mutesa, Marcel Tanner, Agnes Binagwaho, Jamie Forrest, Placide Mbala-Kingebeni, Jean-Jacques Muyembe-Tamfum, Francine Ntoumi, Alimuddin Zumla, Tulio de Oliveira, Edward J Mills
Journal: The Lancet Infectious Diseases (2022)
Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota
Authors: Libin Pan, Hang Yu, Jie Fu, Jiachun Hu, Hui Xu, Zhengwei Zhang, Mengmeng Bu, Xinyu Yang, Haojian Zhang, Jinyue Lu, Jiandong Jiang, Yan Wang
Journal: Acta Pharmaceutica Sinica B (2022)

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.
RGD peptide modified platinum nanozyme Co-loaded glutathione-responsive prodrug nanoparticles for enhanced chemo-photodynamic bladder cancer therapy
Authors: Ying Hao, Yuwen Chen, Xinlong He, Ruxia Han, Chengli Yang, Tailuo Liu, Yun Yang, Qingya Liu, Zhiyong Qian
Journal: Biomaterials (2022)
Machine learning-based marker for coronary artery disease: derivation and validation in two longitudinal cohorts
Authors: Iain S Forrest, Ben O Petrazzini, Áine Duffy, Joshua K Park, Carla Marquez-Luna, Daniel M Jordan, Ghislain Rocheleau, Judy H Cho, Robert S Rosenson, Jagat Narula, Girish N Nadkarni, Ron Do
Journal: The Lancet (2022)
Leucine-973 is a crucial residue differentiating insulin and IGF-1 receptor signaling
Authors: Hirofumi Nagao, Weikang Cai, Bruna B. Brandão, Nicolai J. Wewer Albrechtsen, Martin Steger, Arijeet K. Gattu, Hui Pan, Jonathan M. Dreyfuss, F. Thomas Wunderlich, Matthias Mann, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2022)

Insulin and IGF-1 receptors (IR and IGF1R) are highly homologous and share similar signaling systems, but each has a unique physiological role, with IR primarily regulating metabolic homeostasis and IGF1R regulating mitogenic control and growth. Here, we show that replacement of a single amino acid at position 973, just distal to the NPEY motif in the intracellular juxtamembrane region, from leucine, which is highly conserved in IRs, to phenylalanine, the highly conserved homologous residue in IGF1Rs, resulted in decreased IRS-1/PI3K/Akt/mTORC1 signaling and increased Shc/Gab1/MAPK cell cycle signaling. As a result, cells expressing L973F-IR exhibited decreased insulin-induced glucose uptake, increased cell growth, and impaired receptor internalization. Mice with knockin of the L973F-IR showed similar alterations in signaling in vivo, and this led to decreased insulin sensitivity, a modest increase in growth, and decreased weight gain when mice were challenged with a high-fat diet. Thus, leucine-973 in the juxtamembrane region of the IR acts as a crucial residue differentiating IR signaling from IGF1R signaling.